The clinical hallmark of disseminated gonococcal infection (DGI), a disease of current medical importance, is an arthritis syndrome in which gonococci, per se, are neither easily nor consistently demonstrated in the joint lesions themselves. The objective of the proposed research is to define some of the pathogenetic factors which may underlie this condition. Our hypothesis is that soluble fragments of gonococcal peptidoglycan (PG), released from the bacterium as a function of cell wall turnover or produced by the action of host PG hydrolase, interact with components of the host immune system to initiate the inflammatory reaction associated with DGI. We will test this hypothesis by (1) chemically characterizing and purifying the PG fragments that could most likely interact with the host, (2) testing the ability of these substances, in vitro, to participate in reactions associated with inflammation, e.g., induce and react with antibody, fix complement directly or via the formation of immune complexes, and attract white blood cells, and (3) examining the in vivo correlates of these parameters in patients with DGI. We feel that the postulated role of PG in gonococcal arthritis might also operate in a number of other destructive inflammatory conditions.